The protozoans Trypanosoma brucei and Leishmania species are parasites of humans. T. brucei causes human African trypanosomiasis, and Leishmania infections manifest as a range of symptoms from cutaneous lesions to visceral disease. New drugs are needed for chemotherapy of these tropical diseases, because drugs in current use are dated and can be very toxic. We study the molecular and cell biology of these parasites with the goal of unearthing pathways can be exploited for drug discovery and development. Our studies of protein import into the endoplasmic reticulum of T. brucei, and intracellular signaling in the parasite have led to discovery of several novel anti-trypanosomal lead drugs.